CASP6 Knockout Ca Ski Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the Ca Ski human cervical carcinoma cell line. This product consists of a heterogeneous pool of cells carrying targeted disruptions in the CASP6 gene, enabling robust loss-of-function analyses. The polyclonal format captures a spectrum of genetic lesions, avoiding clonal artifacts and providing a reliable model for investigating caspase-6 biology.
The Ca Ski parental line is an adherent epithelial cell line established from an epidermoid carcinoma of the cervix, and it harbors an integrated HPV16 genome. These cells express HPV oncoproteins E6 and E7, which inactivate p53 and Rb tumor suppressors, driving cell transformation and resistance to apoptosis. Widely used in cancer research, Ca Ski cells provide a relevant context for studying apoptosis and drug responses in HPV-positive malignancies.
CASP6 encodes an executioner caspase that acts downstream of initiator caspases CASP8, CASP9, and CASP10, frequently requiring phosphorylation for activation. Once active, CASP6 cleaves downstream targets including Lamin A/C, PARP, CASP3, and CASP8, amplifying the cell death signal. Its proteolytic function is regulated by interactions with inhibitors like XIAP and c-FLIP, and is influenced by chaperones such as Hsp90. Additionally, CASP6 interfaces with p53 and Bcl-2 family proteins, linking it to both intrinsic and extrinsic apoptosis, as well as necroptotic and neuroinflammatory pathways.
In Ca Ski cells, where HPV-driven inhibition of p53 already impairs apoptosis, CASP6 knockout further disrupts executioner caspase activity, likely enhancing chemoresistance. This model is ideal for dissecting how loss of CASP6 cooperates with viral oncoproteins to promote survival, and for identifying conditions that restore apoptotic sensitivity in cervical cancer.
Applications include high-throughput screening for caspase activators, cytotoxicity assays (MTT), apoptosis assays (Annexin V/PI), and caspase activity measurements using fluorogenic substrates. Additional techniques such as Western blotting for cleavage products, qPCR for downstream targets, and migration/invasion assays support mechanistic studies. Researchers can employ this model to investigate apoptosis resistance in HPV-positive cancers and evaluate therapeutic strategies. For technical support, please contact Ascent Research.
